WO2020171255A1 - Clostridium scindens strain having inhibitory effect against clostridium difficile growth - Google Patents

Abstract

The present invention relates to a Clostridium scindens SNUG 40402(KCTC 13277 BP) strain having an inhibitory effect against Clostridium difficile growth.

Description

Clostridium syndense strain having a growth inhibitory effect of Clostridium difficile

The present invention relates to a Clostridium difficile infection (CDI) treatment pharmaceutical composition comprising the Clostridium strain or a culture thereof having a growth inhibitory effect of Clostridium difficile.

CDI (Clostridium difficile infection) is an antibiotic-related diarrhea disease that occurs when the composition of the normal flora changes in the intestinal tract of a patient receiving antibiotics, and Clostridium difficile proliferates and simultaneously secretes toxins. antibiotics-associated diarrhea, AAD).

C. difficile shows relatively high resistance to disinfectant treatment such as alcohol, and it is difficult to properly manage and remove because it can build spores that can survive in extreme environments for many years or more. According to a recent report by the US CDC, the number of CDI patients per year is around 500,000, and the death toll is 14,000 a year, a serious disease. In general, recurrence is frequent even after treatment. In particular, recurrence patients are classified as a major disease because it is difficult to see great efficacy even with general antibiotic treatment.

Currently, the standard treatment used for CDI treatment is antibiotic prescription, which is known to show relatively low treatment success rate and high recurrence rate. Briefly, Metronidazole and vancomycin both have a limited treatment success rate at the time of primary treatment and show a recurrence rate of 20 to 30%, the treatment success rate at the first recurrence is 70%, and at more recurrences it decreases to 35%, but due to highly toxic strains. Inadequate for use in refractory severe CDIs and recurrent CDIs. In addition, Fidaxomicin inhibits the synthesis of C. difficle toxins A and B and sporulation, and the recurrence rate is also low compared to other antibiotics, but the price is high, and nausea, vomiting, fever, dizziness, and increased liver enzyme levels are still problematic. The possibility of Nitazoxanide as a treatment has also been suggested, but related studies are still insufficient. In recent years, a non-antibiotic approach using fecal microbiota transplantation (FMT), vaccines, and administration of key microbiota as the prevention and treatment of CDIs has been suggested. FMT, in which stool from a healthy donor is administered to the patient's intestine, is one of the treatment methods for refractory or recurrent CDIs. As a result of a synthesis of 28 studies of 317 CDI patients, 92% recovery rate and high recurrence rate. Showed prevention effect. However, FMT therapy has several constraints, such as a procedure that can be unpleasant for the general public to accept, non-standard treatment, and transmission of pathogens, despite a high treatment success rate and low recurrence rate. C. difficile vaccines, including degenerative toxins A and B, are also being studied to be effective in patients with recurrent CDI, but commercialization is expected to take considerable time.

Useful microorganisms isolated in the intestine can cause changes in the intestinal ecosystem and interaction with the immune system, and as a result, maintain space and resource competition with C. difficile. When these are treated, it has been reported that they actually show the same level of therapeutic effect as metronidazole or vancomycin, and that the recurrence rate is also significantly lower (Ollech et al., 2016. Best Practice & Research Clinical Gastroenterology). Therefore, the process of securing and mass-producing functional beneficial strains that can make a big contribution to the prevention/treatment of CDI can be seen as having very important significance as a method that can supplement/replace chemical antibiotic therapy in the future.

Intestinal microbes play a role of protecting the intestinal epithelium from pathogens such as C. difficile, and when an imbalance of intestinal microbes is caused by certain causes such as antibiotics (dysbiosis), the pathogen penetrates the intestinal wall and prevents disease. cause. According to a recent study, IL-25 produced by intestinal microbes increased the tight junction of the intestinal wall to prevent CDI (Buonomo et al., 2016. Cell Reports). It has also been reported that there is a high correlation with the degree of diversity of (Milani et al., 2016. Scientific Reports). As a result of confirming the diversity of intestinal microflora by obtaining clinical samples of CDI patients, it was confirmed that the diversity of intestinal microflora was significantly lower than that of normal people. Secondary bile acids produced by beneficial strains in the intestinal microbiota were C. difficile spores. It has been reported that the growth of C. difficile is inhibited by inhibiting TCA and DCA, which are essential for anger (Winston et al., 2016. Anaerobe.).

An object of the present invention is to provide a Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain, characterized in that it has a Clostridium difficile growth inhibitory effect.

Another object of the present invention is to provide a pharmaceutical composition for the treatment of Clostridium difficile infection (CDI), characterized in that it comprises a Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain or a culture therefor. will be.

Another object of the present invention is to provide a health functional food for alleviating or improving Clostridium difficile infection (CDI), comprising a strain of Clostridium scindens SNUG 40402 (KCTC 13277 BP) or a culture therefor. To provide.

In order to achieve the above object, the present invention provides a Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain, characterized in that it has a Clostridium difficile growth inhibitory effect.

The growth inhibitory effect of Clostridium difficile may be dependent on bile acids.

The concentration of the bile acid may be 0.2 to 2.0% (wt/vol).

In addition, the present invention provides a pharmaceutical composition for the treatment or prevention of Clostridium difficile infection (CDI), characterized in that it comprises a Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain or a culture therefor. .

In addition, the present invention provides a functional food for alleviating or improving Clostridium difficile infection (CDI), comprising a strain of Clostridium scindens SNUG 40402 (KCTC 13277 BP) or a culture therefor. .

The Clostridium difficile infection (CDI) may be a recurrent CDI.

The Clostridium difficile infection (CDI) may be caused by an intestinal microbial imbalance.

In addition, the present invention provides a method for preventing, improving or treating CDI by administering an effective amount of Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain to an individual in need thereof.

In addition, the present invention provides the use of a Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain for inhibiting the growth of Clostridium difficile in an individual.

In addition, the present invention provides the use of a strain of Clostridium scindens SNUG 40402 (KCTC 13277 BP) for the manufacture of a pharmaceutical formulation for preventing, improving or treating CDI.

The present invention relates to a strain of Clostridium scindens SNUG 40402 (KCTC 13277 BP), characterized in that it has a growth inhibitory effect of Clostridium difficile, is effective in CDI treatment and symptom improvement, and , In particular, it is very effective in treating recurrent CDI and improving symptoms.

1 is a result of an experiment on the inhibitory effect of Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain (CS) on C. difficile growth.

2 is a schematic diagram of the establishment of a C.difficile infection prevention model.

Figure 3 is a result of experimenting the body weight change after treatment with Clostridium scindens SNUG 40402 in the C. difficile infection prevention model. Figure 3a is the result of a comparative experiment with the control strain, Figure 3b is the result of measuring the weight change after treatment with Clostridium scindens SNUG 40402, Figure 3c is the result of measuring the change in weight after treatment with Clostridium scindens SNUG 40402 over time.

Figure 4 is a result of testing the C.difficile proliferation inhibitory effect of Clostridium scindens SNUG 40402 in a C.difficile infection prevention model.

Fig. 5 is a result of an experiment on the sensitizing effect of Clostridium scindens SNUG 40402 on C.difficile Toxin in a C.

6 is an experimental result of the effect of reducing colon length induced by C.difficile infection in a C.difficile infection prevention model.

7 is an experimental result of the effect of reducing inflammation in a C. difficile infection prevention model.

8 is an experimental result of the effect of reducing mortality caused by C. difficile infection in a C. difficile infection prevention model.

The present invention provides a Clostridium scindens (Clostridium scindens) SNUG 40402 (KCTC 13277 BP) strain, characterized in that it has a Clostridium difficile (C.difficile) growth inhibitory effect.

Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain was isolated from feces provided by healthy adult volunteers. Since the strain is an absolute anaerobic strain, the separation process was performed under an anaerobic system.

The Clostridium difficile (C.difficile) is a gram-positive bacterium, an anaerobic bacterium, is a relatively large bacterium with a length of 2-17 μm, has a structure such as flagella or projections, and is a bacterium living in human intestine. Clostridium difficile is likely to occur even after administration of antibiotics such as clindamycin, lincomycin, amoxicillin, cefalothin, cefazoline, etc. After the bacterial flora is destroyed, colonization can occur due to toxic C. difficile.

Clostridium difficile produces toxin A (enterotoxin) with a molecular weight of about 310,000 and toxin B (cytotoxin) with a molecular weight of about 270,000. Toxin A first injures the intestinal epithelial cells and then invades the intestinal membrane at the site of toxin B stage and exerts a poison effect.

The growth inhibitory effect on Clostridium difficile strains can be confirmed through an inhibition assay.

The growth inhibition effect may be due to the baiCD gene of a Clostridium scindens strain. The baiCD gene can encode 7 alpha-dehydrogenase. 7 The alpha-dehydrogenase gene can convert cholic acid, a primary bile acid (bile acid), into deoxycholic acid (DCA), a secondary bile acid, and this DAC can inhibit the growth of C.difficile.

In addition, inhibition of growth of C.difficile may be due to inhibition of spore germination.

The Clostridium scindens SNUG 40402 strain is a deposited strain and was deposited with the Biological Resource Center on May 29, 2017, and the accession number is KCTC 13277 BP.

The growth inhibitory effect of Clostridium difficile may be dependent on bile acids.

In the present invention, the concentration of a bile acid capable of exhibiting a growth inhibitory effect of Clostridium difficile may be 0.2 to 2.0% (wt/vol).

The present invention provides a pharmaceutical composition for the treatment or prevention of Clostridium difficile infection (CDI), characterized in that it comprises a Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain or a culture therefor.

CDI may be caused by spore-forming bacteria, specifically Clostridium difficile strain, and may also be accompanied by diarrhea, high temperature, and abnormal pain.

The CDI may be a type of antibiotic-associated diarrhea.

In addition, CDI may have occurred in patients receiving broad spectrum antibiotics (especially clindamycin) that alter the ecological balance of the intestinal flora.

CDI may occur in patients with normal bile secretion in the liver.

In addition, the CDI may be mild CDI, severe CDI, complex CDI, or recurrent CDI, and more preferably, may be recurrent CDI. The severity of the CDI can be determined based on age, whether systemic antibiotics are used, the number of white blood cells, albumin, and serum creatine.

More specifically, in mild CDI, the number of leukocytes may be less than 15,000 cells/ml, and the serum creatine may be less than 1.5 times premorbid level, and in severe CDI, the number of white blood cells is 15,000 cells/ml or more, and serum creatine is 1.5 times premorbid level. It may be abnormal, and complex (complicated CDI) may involve hypotension, shock, rainy season, megacolon, and recurrent CDI may mean recurrence within 8 weeks after successful treatment for CDI.

The pharmaceutical composition according to the present invention can be administered to mammals including humans by various routes. The mode of administration may be any method commonly used, for example, may be administered by oral, dermal, intravenous, intramuscular, subcutaneous, and the like, preferably orally. The pharmaceutical compositions of the present invention are each parenterally in the form of oral dosage forms such as powders, granules, tablets, capsules, ointments, suspensions, emulsions, syrups, aerosols, or transdermal preparations, suppositories, and sterile injectable solutions according to conventional methods. It can be formulated and used as an old formulation. The pharmaceutical composition of the present invention may further contain adjuvants such as a pharmaceutically suitable and physiologically acceptable carrier, excipient, and diluent.

Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium. Silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils. In the case of formulation, diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants can be used.

In an embodiment in which the pharmaceutical composition of the present invention is applied to humans, the pharmaceutical composition of the present invention may be administered alone, but generally, a pharmaceutical composition selected in consideration of the mode of administration and standard pharmaceutical practice. For example, the composition containing the strain of Clostridium syndense of the present invention may be administered in the form of a tablet containing starch or lactose, or in the form of a capsule containing an excipient or alone. It can be administered orally, orally, or under the tongue, in the form of elixirs or suspensions containing chemicals to give off or color.

The dosage of the pharmaceutical composition containing the Clostridium syndense strain of the present invention may vary depending on the patient's age, weight, sex, dosage form, health condition and degree of disease, and at certain time intervals according to the judgment of a doctor or pharmacist. It may be administered in divided doses from once a day to several times. For example, the daily dosage may be 0.1 to 500 mg/kg, preferably 0.5 to 300 mg/kg, based on the content of the active ingredient. The above dosage is an example of an average case, and the dosage may be high or low depending on individual differences. If the daily dosage of the composition containing the mixed extract of the present invention is less than the above dosage, a significant effect cannot be obtained, and if it exceeds that, it is not only uneconomical, but also outside the range of the normal dosage, there is a concern that undesirable side effects may occur. It may occur, so it is better to set it within the above range.

Another example of the present invention is Clostridium scindens (Clostridium scindens) SNUG 40402 (KCTC 13277 BP) strain or CDI (Clostridium difficile infection) alleviation or improvement health functional food comprising a strain or a culture thereof Provides.

The health functional food may be various beverages, fermented milk, food additives, and the like.

The content of the Clostridium syndense strain as an active ingredient contained in the health functional food is not particularly limited appropriately depending on the form of the food, the desired use, etc., and may be added in an amount of 0.01 to 15% by weight of the total food ,

The health beverage composition may be added in an amount of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 ml.

Among the health functional foods of the present invention, there is no particular limitation on liquid ingredients other than those containing the Clostridium syndense strain as an essential ingredient in the indicated ratio as an essential ingredient in beverages, and various flavoring agents or natural carbohydrates, etc. May contain as an additional component.

Examples of the above-described natural carbohydrates are monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose, and the like, and polysaccharides such as dextrin, cyclodextrin, and the like. Sugar and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring agents and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid, and It may contain salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like.

In addition, the health functional food of the present invention may contain flesh for the manufacture of natural fruit juice and fruit juice beverage and vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not so important, but is generally selected from 0 to about 20 parts by weight per 100 parts by weight of the health functional food of the present invention.

Another example of the present invention is that Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain is administered to an individual in need thereof using the Clostridium difficile growth inhibitory effect of the Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain. It provides a method of inhibiting or enhancing the curative ability of an individual including the step of CDI (Clostridium difficile infection), and a method of preventing, improving, or treating CDI.

Another example of the present invention is the use of Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain for inhibiting the growth of Clostridium difficile. It provides the use of the Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain for enhancing the CDI inhibitory or healing ability of an individual, and the use of the Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain for the prevention, improvement or treatment of CDI.

The'individual' refers to an animal that is expected to exert an effect according to the Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain by administering a composition containing the strain or strain according to the present invention as an active ingredient, and the animal includes, for example, dogs, Monkeys, goats, pigs, rats and the like are included, and are preferably humans.

The'prevention' refers to any action of inhibiting or delaying the progress of CDI by administration of a composition comprising the strain or strain according to the present invention as an active ingredient.

The'treatment' or'improvement' refers to any action in which symptoms of CDI are improved or beneficially changed by administration of a composition comprising the strain or strain according to the present invention as an active ingredient.

The'administration' means providing a pharmaceutical composition comprising a predetermined strain or strain according to the present invention as an active ingredient to an individual by any suitable method.

Hereinafter, the present invention will be described in more detail by the following examples or experimental examples. However, the following examples are for illustrative purposes only, and the scope of the present invention is not limited thereto.

Experimental Example 1 . Clostridium scindens SNUG 40402( KCTC 13277 BP) C. difficile of strain (CS) Inhibitory effect on growth

The research team intensively isolated candidate strains from feces provided by more than 40 healthy adult volunteers. Considering that most of the candidate strains are obligate anaerobes, all processes were performed under the anaerobic system of Go Bio Lab.

In the C. difficile growth inhibition experiment, the inhibitory ability of C. difficile was confirmed using the supernatant obtained after culturing the isolated strain for 24 hours. The strains used for the C. difficile inhibitory effect comparison experiment were C. difficile KCTC 5009 strain and C. difficile ATCC43255 strain, and the growth inhibitory effect on the strain was compared. After diluting the OD of the C. difficile strain cultured in the liquid medium for 4 hours to 0.3 and re-inoculating the liquid medium at a concentration of 2%, the CD culture solution and the prepared test strain supernatant were mixed at a ratio of 1:1 at 37°C. Incubated for 24 hours, OD was measured to evaluate the CD growth rate.

Considering that the metabolism of bile affects spore germination and growth of C. difficile, the same experiment was conducted by adding bile of an appropriate concentration to the C. difficile culture medium so that candidate strains can metabolize bile. Observed. The concentration of bile acids in the small intestine of a living body was 0.2 to 2.0% (wt/vol.) (Kristoffersen et al., 2007. Journal of Bacteriology). By adjusting the concentration of bile acid to 0~2.0% (wt/vol.), the effect of inhibiting CDI of the candidate strains in the in vitro environment was confirmed. Specifically, in order to perform the C. difficile viable bacteria inhibition assay (Inhibition assay), the test strain was inoculated into a liquid medium added with bile acids at 0, 0.5, 1% concentration and cultured at 37° C. for 24 hours, and then the supernatant was used. After diluting the OD of the C. difficile strain cultured in the liquid medium for 4 hours to 0.3 and re-inoculating the liquid medium at a concentration of 2%, the CD culture solution and the prepared test strain supernatant were mixed at a ratio of 1:1 at 37°C. Incubated for 24 hours, OD was measured to evaluate the CD growth rate.

As a result, it was confirmed that the CD inhibitory ability of CS increased in a bile acid-dependent manner for two different CD strains (see Fig. 1).

Experimental Example 2 . Mouse model experiment to confirm CDI prevention

In the CDI prophylaxis animal model, C57BL/6 mice that were negatively administered antibiotics for 3 days to disturb intestinal microbial strains were orally administered the candidate strain for 2 days, followed by intraperitoneal administration of clindamycin and infection with C. difficile, resulting in CDI symptoms ( Body weight change) and the efficacy on survival were measured every day for 3 weeks (see Fig. 2).

As a result, in the case of Clostridium scindens SNUG 40402 of the present invention, compared to the infection control group and other Clostridium scindens standard strains, the effect of significantly preventing weight loss was exhibited, and this phenomenon was consistently shown in the recovery phase. (See Fig. 3).

In vivo, in the group fed CS, feces were obtained 24 hours after C. difficile infection, and the degree of proliferation of C. difficile in feces was investigated. To this end, the obtained feces were weighed and suspended in phosphate buffered saline (PBS) prepared anaerobicly, and then the sequentially diluted suspension was spread on C. difficile selective medium and anaerobic cultured at 37°C for 2 days. The number was measured. As a result, Clostridium scindens SNUG 40402 significantly inhibited the proliferation of C. difficile in the intestine compared to infection control and other Clostridium scindens standard strains (see FIG. 4).

To determine whether it is related to the inhibition of C. difficile proliferation and the production of C. difficile toxin, which is the main cause of CDI symptoms, in the group fed CS in vivo, the amount of Toxin A/B in the fecal suspension obtained 24 hours after infection was evaluated. It was analyzed using ELISA kit for quantification of C. difficile toxin.

As a result, in the case of Clostridium scindens SNUG 40402, compared to the infection control group and other Clostridium scindens standard strains, it significantly suppressed the increase of toxins caused by C. difficile in the intestine (see Fig. 5).

On the 3rd day of infection, when CDI symptoms were most severe, the mice were euthanized and the degree of colitis progression was evaluated.

In the case of Clostridium scindens SNUG 40402, compared to the infection control group, the effect of inhibiting the decrease in colon length caused by CD infection was shown (see FIG. 6).

In order to investigate the reduction of colon inflammation caused by CDI, colon tissues of euthanized mice were obtained, RNA-later was used to prevent changes in RNA, and stored in a deep freezer at -80 degrees before analysis. After RNA was extracted from the obtained colon tissue using a Total RNA extraction kit, the expression level of TNF-α, an inflammation inducing factor, among the libraries converted to cDNA using the cDNA synthesis kit was quantitatively analyzed using real-time quantitative PCR.

As a result, it was confirmed that Clostridium scindens SNUG 40402 significantly reduced the expression of TNF-α, a major inflammatory indicator, thereby inhibiting the reduction of the length of the bowel and reducing inflammation in the intestine. (See Fig. 7)

Experimental Example 3 . Mouse model experiment to confirm CDI prevention

In order to confirm the CDI inhibitory effect of C scindens SNUG40402, 10^4 C difficile spores were administered orally, and then the individuals dying from the day of infection were monitored. The graph above was created by integrating the results obtained by repeating a total of 4 times with 4 animals per group. In the case of the PBS-only control group, individuals who died from day 3 to day 6 of infection occurred, resulting in 11 out of 16 deaths, whereas in the group receiving C scindens SNUG40402, only 3 out of 16 deaths. I did. Through this, it can be confirmed that C scindens SNUG40402 lowers the mortality rate due to CDI (see Fig. 8).

[Consignment institution]

Name of donated institution: Korea Research Institute of Bioscience and Biotechnology

Accession number: KCTC13277BP

Consignment Date: 2017529

Claims (12)

1. Clostridium scindens (Clostridium scindens) SNUG 40402 (KCTC 13277 BP) strain, characterized in that it has a growth inhibitory effect of Clostridium difficile.
2. According to claim 1, The Clostridium difficile (Clostridium difficile) growth inhibitory effect is a bile acid-dependent Clostridium scindens (Clostridium scindens) SNUG 40402 (KCTC 13277 BP) strain, characterized in that.
3. According to claim 1, wherein the concentration of the bile acid is 0.2 ~ 2.0% (wt / vol) Clostridium scindens (Clostridium scindens) SNUG 40402 (KCTC 13277 BP) strain, characterized in that.
4. Clostridium scindens (Clostridium scindens) SNUG 40402 (KCTC 13277 BP) strain or a CDI (Clostridium difficile infection) treatment or prevention pharmaceutical composition comprising a strain or a culture therefor.
5. Clostridium scindens (Clostridium scindens) SNUG 40402 (KCTC 13277 BP) strain or CDI (Clostridium difficile infection) alleviation or improvement health functional food comprising a strain or a culture thereof.
6. The pharmaceutical composition for the treatment or prevention of Clostridium difficile infection (CDI) according to claim 4, wherein the Clostridium difficile infection (CDI) is a recurrent CDI.
7. The health functional food for alleviating or improving CDI (Clostridium difficile infection) according to claim 5, wherein the Clostridium difficile infection (CDI) is a recurrent CDI.
8. The pharmaceutical composition for treating or preventing CDI (Clostridium difficile infection) according to claim 4, wherein the Clostridium difficile infection (CDI) is caused by an intestinal microbial imbalance.
9. The health functional food for alleviating or improving CDI (Clostridium difficile infection) according to claim 5, wherein the Clostridium difficile infection (CDI) is an intestinal microbial imbalance.
10. A method of preventing, improving or treating CDI by administering an effective amount of Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain to an individual in need thereof.
11. Use of Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain to inhibit the growth of Clostridium difficile in an individual.
12. Use of Clostridium scindens SNUG 40402 (KCTC 13277 BP) strain for the manufacture of a pharmaceutical preparation for preventing, improving or treating CDI.

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